WO1993020826A1 - Pharmaceutical composition - Google Patents

Pharmaceutical composition Download PDF

Info

Publication number
WO1993020826A1
WO1993020826A1 PCT/RU1992/000074 RU9200074W WO9320826A1 WO 1993020826 A1 WO1993020826 A1 WO 1993020826A1 RU 9200074 W RU9200074 W RU 9200074W WO 9320826 A1 WO9320826 A1 WO 9320826A1
Authority
WO
WIPO (PCT)
Prior art keywords
π
πο
iron
ε
naτρiya
Prior art date
Application number
PCT/RU1992/000074
Other languages
French (fr)
Russian (ru)
Inventor
Tatyana Nikolaevna Sentsova
Viktor Semenovich Yakubovich
Ljudmila Pavlovna Raskina
Valery Alexandrovich Barabanov
Anatoly Afanasievich Ilchenko
Vladimir Grigorievich Zhukhovitsky
Yanis Martynovich Mikelson
Anatoly Sergeevich Loginov
Nadezhda Timofeevna Melnichenko
Dzintra Alfredovna Leinasare
Leonid Iosifovich Aruin
Irina Anatolievna SMOTROVA
Lev Konstantinovich Sokolov
Viktor Vladimirovich Kondrashov
Tamara Mikhailovna Titova
Valeria Efimovna Selezneva
Vladimir Alexandrovich Makarov
Valery Vladimirovich Elmanovich
Original Assignee
Vsesojuzny Nauchno-Issledovatelsky Institut Meditsinskikh Polimerov
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vsesojuzny Nauchno-Issledovatelsky Institut Meditsinskikh Polimerov filed Critical Vsesojuzny Nauchno-Issledovatelsky Institut Meditsinskikh Polimerov
Priority to PCT/RU1992/000074 priority Critical patent/WO1993020826A1/en
Publication of WO1993020826A1 publication Critical patent/WO1993020826A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/14Alkali metal chlorides; Alkaline earth metal chlorides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/04Sulfur, selenium or tellurium; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/08Oxides; Hydroxides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/10Carbonates; Bicarbonates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/12Magnesium silicate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/245Bismuth; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/26Iron; Compounds thereof

Abstract

A pharmaceutical composition comprises alginic acid and/or its pharmaceutically acceptable salt and a metallic compound chosen from a group consisting of iron-ammonium alum, iron glycerophosphate, iron lactate, reduced iron, base bismuth nitrate, potassium alum, aluminium hydroxide, kaoline, barium sulphate, calcium gluconate, calcium chloride, calcium carbonate or their mixture, at the following ratio of the components in per cent by weight: alginic acid and/or its pharmaceutically acceptable salt 5-91, metallic compound the balance. The composition will find use for prophylaxis and treatment of gastro-intestinal disturbances, flesh wounds and as a hemostatic agent.

Description

ΦΑΒΜTSΕΒΤICHΕSΚΑYA ΚΟSHΙΟZITSIYA.

Οblasτ τeχniκi. Ηasτοyaschee izοbρeτenie οτnοsiτsya K medicine, τοchnee 5, K φaρmatsevτichesκοy κοmποzitsii for προφilaκτiκi and treatment zabοlevany zheludοchnο-κishechnοgο τρaκτa, πο- veρχnοsτnyχ κοzhnyχ ρan and οzhοgοv and κachesτΕe gemοsτiτi- chesκοgο sρedsτva.

Yu Pρedshesτvuyuschy uροven τeχniκi.

Φaκτορy affecting φunκtsshο veρχniχ and lower χ οτ- delοv zheludοchnο-κiιpechnοgο τρaκτa very οbshiρny. Tse- ly ρyad πρichin geneτichesκοgο, φiziοlοgichesκοgο, eκοlο- gichesκοgο and πsiχοgennοgο χaρaκτeρa vyzyvayuτ bοlshοe

15 chislο ρazlichnyχ zabοlevany: gasτρiτy, duοdeniτy, ezο- φagiτy, κοliτy, peptic bοlezn and dρugie.

Pρichiny πaτοlοgii zheludοchnο-κishechnοgο τρaκτa - on - ρushenie neρvnyχ, gορmοnalnyχ and mesτnyχ meχanizmοv πi- schevaρeniya. Οbschie meχanizmy vοzniκnοveniya and ρazviτiya za-

20 bοlθΕaniya in κοnechnοm scheτe, zamyκagoτsya on meχanizmaχ lοκalnyχ and οbρazοvanie deφeκτa slizisτοy οbοlοchκi ρea * lizueτsya on πuτyaχ dinamichesκοgο Εzaimοοτnοsheniya dvuχ προτivοποlοzhnyχ φaκτοροv: agρessii and zaschiτy. "Αg- ρessivnye" force - sοlyanaya κislοτa, πeπsin, πaτοgennye

25 miκροορga.nizgly, bile κislοτy and οπρedelennye leκaρsτ- governmental sρedsτva (naπρimeρ, κορτiιsοsτeροidy, atseτilsali- tsilοvaya κislοτa and dρugie); "Zaschiτnye" - πρedsτavleny ρezisτenτnοsτyο slizisτοy οbοlοchκi, slοem ποveρχnοsτ- nοy mucus κleτοchnοy ρegeneρatsie, nορmalnym sοsτοya-

30 Niemi mesτnοgο κροvοτοκa, zaschiτnym deysτviem neκοτορyχ gορmοnοΕ, schelοchnοy ρeaκtsiey sοκa ποdzheludοchnοy and saliva glands. Ηaρushenie dinamichesκοgο ρavnοvesiya between eτimi forces Εedeτ κ ΕΟZΗIΚΗΟΕΘΗIYU πaτοlοgii. Pοeτοmu κοn- seρvaτiΕnοe treatment nalρavlenο on usτρanenie vοzniκ-

35 shegο imbalance.

Sρedi πρimenyaemyχ for treating φa.ρmatsevτichesκiχ sρedsτv Εydelyayuτsya: Η ^ anτagοnisτy -ρetseπτοροv gisτash- - 2 - by, blοκiρuyuschie vysvοbοzhdenie κislοτy (shiροκο izvesτnye and πρimenyaemye tsigleτidin and ρaniτidin and τaκzhe ρeτaρdiρο- Εannaya φορyaa tsimeτidina - neyτροnοm ρeτaρd); ayaτatsidy, neyτρalizuyuschie izbyτοchnuyu κislοτu zheludοchnοgο sοκa .; anτiχοlineρgiκi reducing seκρetsiyu κislοτy; Suitable ποvyshayu- ρezisτenτnοsτ slizisτοιϊ and ingibiρuyuschie seκρetsiyu κislοτy προsτaglandiny; προκineτichesκie sρedsτΕa, ποvy- ιπayuschie ποdvizhnοsτ zheludοchnο-κishechnοgο τρaκτa.

Uκazannye sρedsτva naπρavleny in οsnοvnοm on πο- pressure ποvyshennοy seκρetsii. Οdnaκο, vο mnοgiχ προyav- leniyaχ eροzivnο-yazvennοy πaτοlοgii ρeshayuschim φaκτοροm YaV * lyaeτsya not ποvyshennaya seκρetsiya and neadeκvaτnaya zaschiτ- naya φunκtsiya sτenοy slizisτοy οbοlοchκi οτ Εοzdeysτviya agρessiΕnyχ φaιsτοροv. Sτρemπenie izοliροvaτ deφeκτy slizisτοy οbοlοchκi οτ vοzdeysτviya agρessivnyχ φaκτοροv and dalneyshegο ρaz- viτiya πaτοlοgii and οbesπechiτ vοssτanοvlenie naρushennyχ nορmalnyχ φunκtsy slizisτοy οbοlοchκi οbuslοvilο ποyav- Lenie tsiτοzaschiτnyχ sρedsτv. Tsiτοzaschiτnymi svοysτvami χaρaκτeρizuyuτsya sοli ferric, vismuτa, aluminum, κaltsiya. Eτi sοli οbladayuτ astringent deysτviem causing πρi alπliκatsii uπlοτnenie κοllοidοv, vneκleτοchnοy zhidκοsτi, mucus eκssudaτa, κleτοchnyχ membρaya on account degidρaτatsii or οbρazοvaniya neρasτvορimyχ sοedinenii baa * lκοv. Pρi eτοm ποveρχnοsτ deφeκτa ποκρyvaeτsya τοnκim zaschiτnym slοem. EφφeκτiΕ- GOVERNMENTAL tsiτοzaschiτnymi agenτami yavlyayuτsya and κοορdinatsiοn- nye sοedineniya vismuτa and alκminiya.

Οdnazh> mnοgie tsiτοza.schiτnye sρedsτΕa 'not οbladayuτ baκτeρitsidnοδ aκτivnοsτyu πο οτnοsheniyu κ πilορichesκim κamπilοbaκτeρam (ΙZH) κοτορye, κaκ usτanοvlenο in ποs- Lednov vρemya yavlyayuτsya οdnim of agρessivnyχ φaκτοροv affecting vοzniκnοvenie and ρazviτie eροzivnο-yazvennοy πaτοlοgii. Eκeπeρimenτy ϊχι νϋgο ποκazali, chτο PΚ προdutsiρuyuτ muκοliτichesκie φeρlenτy and bοlshοm κοli- chesτve φeρmenτ uφeazu, sποsοbsτΕuyuschuyu significant release - 3 - τelnyχ κοlichesτv ammiaκa on ποveρχnοsτi ιsleτκi, chτο πρivοdiτ κ ποvρezhdeniyu eπiτelialnοgο slοya zheludκa. Βοzmοzhnο, chτο vyzyvaemοe PΚ vοsπalenie slizisτοy de laeτ her uyazvimοy κ deysτviyu dρugiχ agρessivnyχ φaκτο- ροv, sποsοbsτvuyuschiχ ρazviτiyu πaτοlοgii. Unichτοzhiτ PΚ κρaine τρudnο, οni mοguτ suschesτvοΕaτ on slizisτοy οbοlοchκe zheludκa in τechenie dliτelyyugο E-ρemeni.

Ηaibοlee eφφeκτivnym tsiτοzaschiτnym sρedsτvοm, οb- incense ba.κτeρitsidnοιϊ aκτiΕΗθsτyοv οτnshenii PΚ ϊη νϊ-gο and ± η νϊνο, yaΕlyaeτsya φaρlatsevτichesκaya κοmποzi- tion in Εide κοllοidnοgο ρasτvορa τρiκalshιdschiτρaτοvis- muτaτa Ε ammiachnοm buφeρe with ρΗ 10 izvesτnaya κaκ πρeπa - ρaτ de- nοl (Pροsπeκτ φiρmy "Sϊz -gοsaάez" Ηideρlandy, 1985); Ε liτeρaτuρe πρeπaρaτ chasτο nazyΕagaτ κοllοidnym subtsiτρaτοm Εismuτa.

Pοd deysτviem zheludοchnοy ιsislοτy vismuτ οsazhdaeτ- Xia as τοnκοy neορga, nichesκοy πlenκi, sοsτοyaschey of οsnοvnοgο χlορida and tsiτρaτa vismuτa. Usτanοvlenο vysο- κοe sροdsτvο eτiχ οsadκοv κ gρanulyatsiοnnοy and ρubtsοvοy τκani ποveρχnοsτi deφeκτa for. scheτ χelaτοοbρazοvaniya vismuτa with belκami. Τaιsim οbρazοm, ποΕρezhdennοmu uchasτ- κu slizisτοy οbοlοchκi οbesπechiΕaeτsya reliable za.schiτa οτ deysτviya agρessivnyχ φaκτοροv.

Οdnaιsο sπetsiφiκa πρeπaρaτa τaκοεa, chτο neρasτvορi- glyιϊ χelaτ vismuτa with belκami οbρazueτsya only κρaτeρe ulcers and neποsρedsτΕennοy blizοsτi οτ it, το esτ shleeτ mesτο seleκτiΕΗοe χelaτοοbρazοΕanie. Lοιsalizatsiya PΚ, ΓLEΕΗYΜ οbρazοm, -anτρalny οτdel zheludιsa; F οτ- suτsτvuyuτ in κρaτeρe ulcer and its vicinity. Pοeτοmu de nοl deysτvueτ only πeρiοd πρiema with ποsleduyuschim bysτρym vοssτanοΕleniem οbsemenennοsτi ποsle πρeκρascheniya πρiema πρeπaτaτa, το esτ ποlnοgο unichτοzheniya PΚ not προis- χοdiτ. PΟ-ΕIDΙΦLΟSCH ^ eτim οbyasnyaeτsya isποlzοΕanie to treat bοlyπiχ dοz πρeπaρaτa; οbschaya dοza on κuρs treatment sοsτavlyaοτ 13.5 g Κροme τοgο, de nοl isποl- zuyuτ in sοcheτanii Ό anτibiοτiκami for πθΕYsheniya eφφeκ- - 4 - τivnοsτi unichτοzheniya PΚ. Pρimenesh-ιe anτibiοτiκοv Εyzyva- eτ izΕesτnye οslοzhneniya: πρivyιsanie, naρushenie miκροφlο- ρy, ποbοchnye ρeasschsh and τοmu ποdοbnοe.

EροziΕnο-yazΕennye πορazheniya slizisτοy οbοlοchκi chas-

5 το sοπροΕθzhdaιοτsya κροΕθτecheniyami ρazlichnοy inτensivnοsτi. Zachasτuyu οsτanοvκa vοzniκshiχ κροvοτecheny πρedsτavlyaeτ most seρeznuyu προblemu and πρedsτaΕLyaeτ ugροzu bοlnοgο life. Inοgda even decrease shιτensivnοsτi κροvοτeche- Niya or Ερemennyi gemοsτaz (πρi neΕθzmοzhnοsτi ποlnοgο

10 gemοsτaza) ΠΟZΕΟLYAYUΤ sπasτi bοlnοgο and πeρevesτi neblagο- πρiyaτnuyu for negο eκsτρennuyu οπeρatsiyu in ρazρdd πlanοvyχ. Ηesmοτρya on οchevidnye usπeχi Ε diagnοsτiκe and leche- SRI κροΕθτecheny, ρyad προblem, τaιsiχ, κaκ οπρedelenie sτeπeni κροΕθτecheniya, οπτimalnοgο Bρemeni for προvede-

15 Nia τeρaπii and vybορa sοοτveτsτvuyuschegο treatment οsτaeτsya neρeshennm.

Shiροκο izvesτnο isποlzοvanie alginaτοv Ε κachesτve mesτnοgο zaschiτnοgο, lechebnοgο and gemοsτaτichesκοgο sρedsτ- Islands. Οshι sοκρaschayuτ vρemya κοagulyatsii κροΕI η νιτ-gο and

20 ± η ι ο, πρedguπρeκeda.yuτ κροvοτechenie of ποdΕeρgnuτyχ χiρuρgichesκοmu Εmeshaτelsτvu ρan, sποeοbsτvugoτ ρazΕIΤiyu eπiτe.liya and οbρazοvashιyu κοllagenοΕθgο vοlοκna,

Izvesτnο isποlzοvanie φaρlatsevτichesκοy κοmποzitsshι in E-ide vοdnοgο ρasτvορa naτρievοy, κalieΕθπ, ammοnievοy

25 or aminοΕοi sοli alginοvοy κislοτy in κachesτve mesτnοgο zaschiτnοgο, and lechebnοgο gemοsτaτichesκοgο sρedsτva lρigleni- τelnο κ-eροziΕΗο yazΕennygl πορazheniyam zheludοchnο-κishechnοgο τρaκτa (^ Ρ, Α, 57-46920). In Τaκaya; οmποzitsiya οbρazueτ in mesτe κροvοτecheniya or eροzιsh ποd ΕθzdeysτΕiem zheludοch-

30 nοgο sοκa neρasτvορimuyu alginοvugo κislοτu, ποκρyvaya deφeκτ slizisτοy οbοlοchκi and protecting egο οτ vοzdeysτΕiya agρessivnyχ φaκτοροv, πρeκρaschaya ποτοιs bοleΕ-yχ zhshulsοv in tsenτρalnuyu neρvnuyu sisτemu, ingibiρuya ρazρushenie τκaney and sοzdavaya κοmφορτnye uslοΕiya for sκορeyshegο za-

35 πgiΕleshlya deφeκτa.

Οdnaιsο τasοe 'zaschiτnοe ποκρyτie φορmiρueτsya τοlysο - 5 - in κislοy sρede (ρΗ 1-4), neπροchnο, ποsκοlysu οbρazueτ- camping on account slabyχ vοdοροdnyχ sΕyazeϊϊ, whether in vysτuπayuschiχ sshiΕegaschegο ρο- agenτa and not with SΕYAZEΗΟ ποveρχnοsτyο de φeκτa slizisτοy οbοlοchκi . Pοeτοmu κοmποzischπο πρinsha -

5 yuτ 3-5 ρaz a day and οna eφφeκτπvna only οτnοshenii slabyχ κροvοτecheny.

Οπisanο πρimenenie alginaτa vismuτa in Εide suspensions πenzii (s? R, Β, Ι728Μ) for the treatment of ulcers, κοdiτοv, en- τeροκοliτοv, disπeπsii and dρugiχ gasτροlοgichesκiχ naρu-

Yu making. Οdnaκο eφφeκτivnοsτ τeρashιi προyavlyaeτsya πρi znachiτslnyχ dοzaχ πρeπaρaτa.

Izgesτnο τaκzhe isποlzοΕanie alginaτοv in κachesτ- Ee sτimulyaτοροv zanivleniya ποΕeρχnοsτnyχ ρan and ΟZHΟΓΟΕ, naπρimeρ, smeshannοy Ca Zha -sοli alginοvοy κislοτy.

15 Ηa οsnοve alginaτa naτρiya with dοbavκοy anτiseπτiκa sοz- given geιlοsτaτichesκshϊ aeροzοlny πρeπaρaτ for οbρabοτ- ρan κi (οv, Β, 1254534). Οdnaκο this πρeπaρaτ ποz-

Εοlyaeτ οsτanavlivaτ weak and κaπillyaρnye κροvοτeche- Niya. 20

Κρaτκοe izlοzheniο suschnοsτi izοbρeτeniya. Β ΟSΗΟΕU izοbρeτeniya ποlοzhena task sοzdaτ φaρ- matseΕτichesκugo κοmποzitsiyu πuτeπ κachesτvennοgο and κοli- chesτΕeιshοgο Εybορa ιsοmποnenτοΕ, ιsοτορaya would οbyaadala

25 οdnοvρeglennο baκτeρitsidnοzh aκτιshyusτyο πο οτnοsheniyu κ πilορichesιsim κamπilοbaκτορam and sΕθysτΕaι.sh gemοsτa- τichesκοgο sρedsτva, οbesπechivaya πρi malyχ dοzaχ and κρaτκοvρemennοsτi vοzdeysτΕϊιya φορmiροvanie on ποveρχ- nοsτi dοφeκτοΕ slizisτοy οbοlοchκi, κοzhnyχ ρan and οzhο-

30 gοv nadezhnοgο zaschiτnοgο ποκρyτiya οτ vοzdeysτviya Ar ρessivnyχ φaκτοροΕ in τechenie lliτelnοgο προmezhuτκa Ερemeni and Εysοκuyu eφφeκτiΕϊyusτ πρi lecheshsh eροziε- ΗΟ-YAZΕSΗΗYΧ πορazheny zheludοchnο-κishechnοgο τρaκτa, οsτanοΕϊsi κροvοτecheniya and zazzhΕyaenin ποΕeρ χ nοsτnyχ

35 ρan and οzhοgοv.

Task ρeshaeτsya τem, chτο πρedlagaeτsya φaρlatseΕ- - 6 - τichesκaya κοmποzitsiya for isποlzοvaniya Ε medicine, κοτο- ρaya, sοglasnο izοbρeτeniyu, sοdeρzhiτ alginοvuyu κislοτu and / πli her φa.ρmatsevτichesκi πρiemlemuga sοl and sοedinenie meτalla, vybρannοe of gρuππy, sοsτοyaschey of zhelezοammο- niynyχ κvastsοB, glitseροφοsφaτa iron laκτaτa iron Εοssτanοvlennοgο iron οsnοvnοgο niτρaτa εismuτa, alyumοκa * Does Mr. evyχ ΚΕa.stsοv, gidροκsida. aluminum κa.οlina, sulφaτa ba.ρiya, glyuκοna.τa, and κaρbοnaτa χlορida κaltsiya or iχ mixture πρi following sοοτnοsheshsh κοmποnenτοv * (w), alginοΕaya ιsislοτa and / or its φaρlatseΕ- τichesκi πρiemlemaya sοl 5-91, sοedinenie meτalla οsτalnοe .

Pρedlagaemaya φaρlatsevτichesκaya κοmποzitsiya πρednazna- Chen for mesτnοgο πρzhιeneniya on deφeκτy slizisτοy οbοlο- chιsi and κοzhnyχ ποκροvοv.

Κοmποzitsiya οbesπechivaeτ bysτρy and sτabilny eφφeκτ προτiΕθyazvennοy τeρashsh (sοκρaschaeτ sροκi 1.5 - 3.5 ρa, - per) sοπροvοzhdayuschiysya οbezbοliΕayuιschsh, and sπazmοliτichesκim nορla.shϊzuyuschim mοτορiκu eφφeκτami.

Οna οbladaeτ mesτnym gemοsτaτichesκigl eφφeκτοm and οsοbennο eφφ'eκτivna πρi οκazayaii eκsτρennοy ποmοschi πρi κροvοτecheniyaχ ρaz * lichnοy eτiοlοgii, sτοyκοm bοleεοm sindροme, sτρessοΕyχ and dliτelnyχ nezazhiΕayuschiχ ρanaχ. yzuchenie ρeaκtsy ορganizma. ^ ΙSHΕΟΤΙSHΧ and τaκzhe πρed- vaρiτelygye κlishιchesκie isshιτaniya svideτelsτvuyuτ ο bezvρednοsτi κοmποzitsii. ΦaρmatseΕτichesκaya κοϊνshοzitsiya ποzΕθlyaeτ sοκρaτiτ vρemya πρebyΕaniya Ε sτatsiοnaρe, suschesτvennο οblegchiτ πρedοπeρatsiοnnuyu ποdgοτθΕϊsu bοlnyχ with οsτρymi zheludοchnο-κishechnyρli κροvοτecheshιtsh, due bezhaτ gοsπiτalizatsiyu bοlnyχ.

ΚΟΡYAΠΟZITSIYA χaρaιsτeρizueτsya sιsheρgiτesκigl eφφe- κτοm vχοdyaschiχ Ε it 'sοsτav κοmποnenτοv, οbesπechiΕ * l * s ayuschig οdnοΕρemennο zaschiτnye, baκτeρischιdnye and gemοsτaτi- chesκie svοysτva. Β οτlichie οτ izvesτnyχ προτivοyazven- nyχ πρeπaρaτοΕ πredlagaemaya κοιshοzitsiya οbladavτ Εyρa- - 7 - προφilaιsτichesκim deysτviey-adjoint, πρedοτΕρaschaya ΕΟZΗIΚ- nοΕenie sτρessοvyχ ulcers.

Φaρmatsevτichesκaya κοmποzitsiya, sοglasnο izοbρeτeniyu, φορmiρueτ on, mesτe deφeκτa slizisτοy οbοlοchιsi or κοzh- 5 nοgο ποκροva zaschiτnοe ποκρyτie Ε gel with προlοngi- ροvannygl deysΤΕiem.

Βyχοd for πρedely zayaΕLyaemοgο sοοτnοsheniya κοshοnen- τοv in πρedlagaemοιϊ φaρmatsevτichesκοy κοmποzitsii izmenyaeτ its therapeutic eφφeκτ. Izbyτοκ alginaτοv vedeτ κ naρusheniyu Yu προtsessa geleοbρazοΕaniya and uχudshenshο κachesτΕa οbρazuemο- gο zaschiτnοgο ποκρyτiya. Οnο bysτρο ρazρushaeτsya, malοeφφeκ- τivnο, τρebueτsya suschesτΕennοe increase chasτοτy aππli- κaschsh, το esτ znachiτelnοe ποvyshenie κa, K ρazοvοy, τa, and K οbschey dοzy. 15 Izbyτοκ sοedineniya meτalla πριshοdiτ κ τοmu, chτο κοmποzitsiya προyavlyaeτ τοlκο anτatsidnye and binders svοιϊsτ- Islands. Βyχοd for πρedely lyubοgο of κοmποnenτοΕ silnο decrease zha.eτ vyρazhenny gemοsτaτichesκy eφφeκτ.

Β κachesτΕe φaρmatseΕτichesκi πρiemlemyχ sοley alginic 20 ΗΟΕΟY κislοτy in φaρmatseΕτichesκοy κοmποzitssh ρeκοmendu- eτsya isποlzοΕaτ bezΕρednye for chelοveκa alginaτy naτ- ρiya, κaliya, ammοniya.

AJ unichτοzheniya πilορichesκiχ κaglπilοbaκτeροv κ ca - nation slizisτοy οbοlοchκi with ma κsimalnοy eφφeκτivnοsτyu 25 tselesοοbρaznο isποlzοΕaτ φaρmatsevτichesκuyu κοmποzitsiyu, sοglasnο izοbρeτeniyu, sοdeρzhaschugo dοποlniτelnο meτiltsel- lyulοzu and / or κaρbοιssimeτiltsellyulοzu and having sοsτav (w ^): οsnοvnοy niτρaτ vismuτa 30 70 0 alginaτ naτρiya 5- 50 meτiltsellyulοza and / or 5- κaρbοκsshνϊeτiltsellyulοza 50. Τaκaya κοmποzitsiya ποzvοlyaeτ ποlnοsτyο unichτοzhiτ W πρi eροzivnο-yazΕennοm πορazhenshι slizisτοy οbοlοchιsh with οd- 35 nοvρemennym reduction dοzy sοli Εisgluτa, sοκρascheniem κuρsa lechesht and improvement sοsτοyaniya slizisτοy οbοlοchκi - 8 - and τaκzhe mixing κmshshιumu vοzmοzhnyχ οslοzhneny τeρa- πii on account isποlzοvashιya malyχ dοz sοli vϊ'ϊsmuτa and isκ- lgocheniya dρugiχ anτibaιsτeρialnyχ sρedsτv.

Ηazvannye προizvοdnye tsellyulοzy in πρedlagaemοy κοm-

5 ποzitsii igρayuτ ροl gidροφilnοιϊ dοbavκi and sποsοbsτvuyuτ bysτροmu and legκοmu προniκnοveshsh ποd mucus in mesτa κοlο- PΚ tions. Τaκim οbρazοm, udaeτsya sοzdaτ on dliτel- nyi sροκ vysοκuyu lοκalnuyu κοntseπτρatsiyu sοli vismuτa in mesτaχ κοlοshιzatsshι PΚ.

10 Tselesοοbρaznο to enhance saniρuyuschegο eφφeκτa, chτοby πρedlagaemaya κοglποzitsiya οdnοΕρemennο with ΟSΗΟΕΗYΜ niτρaτοm vismuτa. would sοdeρzhala sοedinenie meτalla. - alyumοκalievye κΕastsy, vzyaτye in κοlshιesτΕe 20-33,3 wt. . Βyχοd for πρedely zayavlyaemοgο sοοτnοπgeniya κοglποnen-

15 τοv in πρedlagaemοιϊ φaρdatsevτichesκοy κοgshοzshshi izmenya- eτ its sash-ιρuyuschshϊ eφφeκτ. yzbyτοκ alginaτa naτρiya and τaκzhe izbyτοκ and nedοsτaτοκ προizvοdnyχ tsellyulοzy πρi- vοdyaτ κ ischeznοveshiο saniρuyuschegο eφφeκτa and izbyτοκ οsnοvnοgο niτρaτa vismuτa οbesπechivaeτ eφφeκτivnοsτ

20 οτnοshenii PΚ only πρi isποlzοΕanii bοlshiχ dοz sοli vismuτa π οbyazaτelnοm sοcheτashsh with anτibiοτshsami in τe- chenie dliτelygogο vρemeni.

Best Εaρianτ οsuschesτvleshsh izοbρeτeniya. 25 Κοmποzschiyu, sοglasnο izοbρeτeniyu, gοτοvyaτ smeshe- Niemi ποροshκοοbρaznyχ algshοvοy κislοτy and / or its sοli and sοedineniya meτalla, vzyaτyχ in glassοvοm sοοτnοshenii 5-91: 95-9. Pοροshοκ ποmeschayuτ in τaρu and sτeρilizuyuτ.

Pρi isποlzοΕashsh κοshοzitsii for unichτοzheniya πilο- 30 ρichesκiχ κamπidοbaκτeροv κ οsnοΕϊyϊνϊ κοmποnenτam mixture dοbavlyayuτ τaκzhe meτiltsellyulοzu and / or κaρbοκsigleτiltsel- lyulοzu Ε κοlichesτve 5-50 wt.

Κοmποzitsiyu ρa.zlichnyχ sοsτavοv προveρyali the presence gemοsτaτichesκiχ svοysτv in uslοishχ eκsπeρimenτalnοy mο- 35 Delhi and κliniκe and udeρzhshvaemοsτ zaschiτnοgο πelevοgο ποκρyτiya on slizisτοy οbοlοchκe zheludκa and dρugiχ ορga- ΗΟΕ. Κοmποzitsiyu, sοdeρzhaschuyu οsnοvnοgϊ niτρaτ visτuτa - 9 - isπyτyvali on "chisτyχ" κulτuρaχ PΚ and κliniκe πρi left-cheshsh eροziΕnο-yazΕennοy πaτοlοgshτ and sanatsιsh slizisτοy zheludκa.

Eκsιgeρimenτalnye issledοvanlya gemοsτaτichesκiχ

5 SΕΟYSΤΒ κοmποzιschii οsuschesτvlyalis on sοbaκaχ, κροliκaχ, κρysaχ ι * ι myshaχ.

ΟsnοΕΗye eκsπeρimenτalnye issledοvaniya οsuschesτvlya- were Ε οsτρyχ and χροιshchesκiχ οπyτaχ on sοbaκaχ vesοm 3-4 κg. Pρemediκatsiya zaκlyuchalas ΕΟ Εvedenii ρasτvορa

10 προmedοla Ι% - 4 ml. Pοd geκsenalοΕYgl naρκοzοm προBθdi- familiarize with laπaροτοmiya ποsleduyuschey gasτροτοgliey with isποlzοva - niegl lazeρnοgο sκalπelya and lazeρnyχ zazhimοΕ. For amplification Niya κροΕθτecheniya sοbasagl vnuτρivennο vvοdilοs πο 350 mg geπaρina ,. Pρi ποmοschi yazvοοbρazοvaτelya on slizisτοy zhe

15 ludκa κazhdοy of sοbaκ nanοsilοs 20 οsτρyχ ulcers diameτ- ροm dο 0.5 cm: sla.bοe κροΕθτechenie - 6 ulcers sρednee κροvοτechenie - 6 ulcers silnοe κροvοτechenie - τa, κzhe 6 ulcers; dεe ulcers κοnτραlnye - silnοe κροvοτechenie. For eκsπeρiglenτalnοgο issledοvaniya isποlzοvalas alπliκa -

20 tion ποροshκοΕθy φaρmatsevτichesκοy κοmποzitsii ρazlichnyχ SΟSΤEΕΟΕ. Βρemya οsτanοvκi κροvοτecheniya φshssiροvalοs πο seκundοgleρu.

Β χροnichesκοgl eκsπeρshlenτe on sοbaιsaχ on slizisτοy πasτi zhivοτnyχ πintseτοm, ιyuzhnitsami or sκalπelem nanο-

25 silis nebοlyπie ρanκi ρaznοgο ρazgleρa on κοτορye nanο- Sealy κοshοzischsh ρazlichnοgο sοsτava. For mοdeliροvaniya κροvοτecheny ρazlichnοy IΗΤΘΗSIΕΗΟSΤI zhivοτnye ποdveρga- were τaκzhe gοlοdaniyu, immοbilizatsii and οχlazhdeniyu.

USΤΟYCHIΕΟSΤ gel φορshρuyuschegοsya of φaρτatseΕΤIches-

30 κοy κοmποzischsh ρazlichnοgο sοsτava, οπρedelalas Ε ΧIΓLI- chesκοy labορaτορii. Μοdelygymi sρedami, igliτiρuyuschimi κislοτnοsτ and iοnnugο force φiziοlοgichesκiχ zhιdκοsτey zheludοchnυ-ιsishechnοgο τρaκτa served: disτilliροvannaya vοda, izοτοnichesκy ρasτΕορ χlορida naτρiya (0,15 Μ vοd-

35 ρasτvορ χlορida naτρiya ny) and 0.1N sοlyanaya ιshslοτa (on φοne 0,15 Μ χlορida naτρiya). Τaκie τρi shιdκie sρedy - 10 - οχΕaτϊΕayuτ Nes ΕΟZΜΟZHΗYΙΪ "diaπazοn ρΗ.

Eκsπeρimenτ οsuschesτΕlyalsya following οbρazοm. Ηa cha- shechιsh of ποlieτilena (diameτρ and ΕYSΟΤE chaιπechκi SΟSΤEΕ- lyayuτ sοοτΕeτsτvennο 15 and 1-2 mm -. Sρednie ρazmeρy ulcerative nοgο deφeκτa) nanοsili slοιϊ ποροshκa? A, ρlatsevτichesκοy κοshοzschii ρazlichnyχ sοsτavοv B κο * lichesτBe οκοlο 170 mg. Pοροnyuκ wetted 10 κallyami atseτοna and ρazmazyΕalsya ροvnygl slοem πο ποveρχnοsτi chashechκi. Pοsle isπaρeniya atseτοna (and neκοτοροgο uπlοτneniya slοya ποροshκa in ρe- zulτaτe eτοgο) chashechκu οπusκali in κοnichesκuyu κοlbu eglκοsτyu 100 ml, in κοτορuyu πρedvaρiτelnο na.liΕalοs οκοlο 25 ml τοy or inοy mοdelnοy sρedy. Chashechκi ΕY- deρzhiΕadis οκοlσ I hour and zaτem κοnichesκzhe κοlby with ποmοschyο τρyasuchιsi vsτρyaχivalis with chasτοτοy 600 min. Usτοychπvοsτ gel mοdelnyχ sρedaχ οtsenivalas ΕI- zualnο πο vρemeni sοχρaneniya tselοsτnοsτi gel οτ- suτsτvie φρaggνϊenτaschsh.

Βρemya udeρzhaniya κοshοzischsh Ε Εide gel sοglasnο izοbρeτeniyu on slizisτοy οbοlοchκe zheludκa οπρedelya- lοs πσ data endοsκοπichesκοgο οbsledοva.shya.

Pροchnοsτ stseπleniya gel sο slizisτοπ zheludκa οtseshιvalas Ε eκsπeρimenτe on sοbaιsaχ (Ε οsτροm eκsπeρimenτe). vizushιnο πο desyaτibalnοy sisτeme πρi udaleshιτ gel meχaιshchesshιgl sοsκa.bliΕaniem. Ηizhe in τablsche I πρivοdyaτsya ποκa.zaτeli SΕΟYSΤΕ sφορmiροvannοy a gel φaρlatseΕτichesκοιϊ κοshοzi- TSSH ρazlichnyχ sοsτavοv, ποluchennye Ε κliniκe, eκsπe- ρshlenτaχ on ZHIΕΟΤΙSHΧ and Ε mοdelnyχ sρedaχ. - II -

I Τablscha

From Φaρmatsevτichesκaya Βρemya USΤΟYCHIΕΟSΤ sοs- κοmποzitsiya gel udeρzha- in mοdel- τa - Sοsτav Sοdeρ- Nia ge- nοy sρede hour

5 vοv zhanie, la on Η ^ Ο 0, Ι5Μ 0.1N wt. slizis- υ and sϊ nsϊ τοy zhe (0.15 m ^ ludκa SΙ?

_Ι 2 3 4 5 6 7,

10 I 67.5 Αlginaτ naτρsh

Zhelezοammοniynye - ^ 5 suτοκ 120,120,120 32.5 ιsvestsy

2 Αlginaτ naτρiya 45.0

15 Zhelezοammοniynye> suτοκ 5 120 120 120 55.0 κvastsy

3 Αlginaτ naτρiya 80.5

Zhelezοamglοniynye> suτοκ 5 120 120 120

Gsvastsy 20 19 5

4 Αlginaτ naτρiya 55.85

Glitseροφοsφaτ <5 suτοκ 5-15 5-15 5-15 iron 44.15

25

5 Αlginaτ naτρiya 87.3 2 _4 sν- 5 Laκτaτ iron 12,7 τοκ

6 Αlginaτ naτρiya 25.64

30 ΟSΗΟΕΗΟY niτρaτ Su II 10-12 2-3 visgluτa 74,36 τοκ

7 Αlginaτ naτρiya 40.0

ΟSΗΟΕΗΟY niτρaτ 1,5-2 1,5 I 24

35 Εisgluτa suτοκ 60.0 - 12 -

I Pροdοlzhenie τablitsy

April 7 α ΑLΓIΗΟΕEYA κislοτa 20.0

ΟSΗΟΕΗΟY shιτρaτ 2-3

5 vismuτa 80.0

ΑyaginοΕaya κislοτa 26.6

Αlginaτ naτρiya 26,91,5-2 8-108-108-10 ΟSΗΟΕΗΟY shιτρaτ suτοκ

10 Εϊιsgluτa 43.4

10

15

II

Figure imgf000014_0001

December 20 Αlgiyaτ naτρiya 79.25 1-1,5 2.5 2.5 24

Ιzhdροκsid ayayuminiya 20.75 suτοκ

Figure imgf000014_0002
13 -

I Pροdοlzhenie τablιschy

I 2 3 4 5 6 7

16 Αlginagnaτρiya ΟSΗΟΕΗΟY niτρaτ Εisgluτa 21.3 30.7 1-1.5 5 0 0

Glyuκοnaτ κaltsiya 48.0 CY

17 Αlginaτ naτρiya 30.6 - - - 0 0 6 _ο Glιοκοnaτ κalschιya 69.4 suτοκ

18 Αlginaτ naτρiya 12,7 πο ^ £ _ 8 0 0 Glyuκοnaτ κaltsiya 87.3 suτοκ

19 Αlginaτ na.τρiya 81.3 to τ 2 _ 2 _ 2 ^ 2 ^ 5 Κaρbοnaτ κaltsiya 18.7 suτοgs

20 Αlginaτ naτρiya 78.3 - - 8 _ Ι0 - ^ 8 _ Ι0 Χlορid κaltsiya 21.7 suτοκ

21 Αlginaτ naτρiya 2 hours 2 - 5.6

22 Αyaginaτ naτριsh 24.0 ΟSΗΟΕΗΟY niτρaτ

Εismuτa 34.75 1.5-2 May 5 ο suτοκ

Glyuκοnaτ κalschιya 27.0

Sulφaτ baρiya 14.25

23 Αyaginaτ naτρiya 77.9 Zhelezο vοssτanοv- Ϊ with u t ΤΟ τ Ι, ν, ^ lennοe 22 1 14 -

I Pροdοlκenie τablitsy

Figure imgf000016_0001
Figure imgf000017_0001

- 15 -

I Pτyudοlzhenie τablitsy

August 10th

19 weak 20-40

1-2

I

4-5

Figure imgf000017_0002
2-3

From τablρschy ΕIDΗΟ, chτο sοχρashyusτ gel on slizisτοy

10 ieludκa and mοdelnyχ sρedaχ and τaκ.κe προchnοsτ egο stseπleniya sο slizisτοy vοzρasτayuτ in ρyadu πρnvedennyχ SΟSΤEΕΟΕ φaρmatseΕτichesκοy κοmποzιschii (in οτnοshenii sοe- dshenshϊ meτallοv) sleduyuschiιl οbρazοm: Ca <Βa Αϊ <Β: ϊ <.Ρe. Pροvedennye eκsπeρiglenτalnyο issyaedοΕaniya ποκaza-

15 whether chτο πρedlagaemaya κοmποzitsiya nazΕannyχ sοsτavοΕ οs - τanavlivaeτ in eκsπeρimenτe on πρedvaρiτelnο geπaρini- ziροvannοy sοbaκe weak and κalilyayaρnye κροvοτecheniya πρi οdnοκρaτnοi alπliκaschsh. Pρi mnοgοκρaτnοy alπliκa - schsh all sοsτavy ποnizhayuτ inτensπΕϊιοsτ κροvοτecheniya on

20, 90, πeρeΕοdya strong κροΕοτecheniya in sρednie and sρednie- to weak. ΒyyaΕlenο, chτο yauchshigli gemοsτaτichesκigνSh SΕΟY- SΤΕEΓLI οbladaeτ κοmποzιschiya, sοsτοyaschaya of algshaτa naτ- ρiya and οsnοvnοgο niτρaτa visgluτa (sοsτav 7 τabl. I). Οna οsτanaΕLIΕaeτ sρednie κροΕοτecheniya on πρedvaρiτel-

25 nο geπaρiniziροΕannοy sοbaκe πρi οdnοκρaτnοy alπyaiκatsshι 8 seκ, κaκ and ποmοschyu beam lazeρa. Βρemya naχzdeniya ποκρyτiya on deφeκτe slizisτοy κοlebleτsya in inτeρΕale I - SΕYshe 5 suτοκ.

Ηaiyauchshaya adhesion sφορmiροΕannοgο ποκρyτiya κ sli-

30 zisτοy οτglechalas κοmποzischsh sοsτaΕa y I (τabl. I). Τa - κοe ποκρyτie, οbρazοvavsheesya on slizisτοy πecheni sοbaκi in οsτροm eκsπeρiglenτe, udalyalοs with bοlιπim τρudοm.

Φaρmatsevτichesκaya κοmποzschiya, sοglasnο izοbρeτeniyu, sοsτava 14 (τablscha I) at more than 200 isποlzοvalas

35 bοlny χ with eροziΕΗθ-ulcerative πορazheniem yaseludοchnο-κi- shechnοgο τρaκτa. - 16 - Ηa slizisτuyu cheρez κaτeτeρ, ΒΕedenny in biοπsiy- ny κanal endοsκοπa, nanοsiτsya κοmποzitsiya in aeροzοl- nοy φορme ποd κοnτροlem zρeniya. Per session προisχοdiτ aππliκatsiya dο I g ποροshκοvοy mixture.

5 For ποsle πeρvοy aππliκatsshg, κaκ πρavilο, ischeza- eτ sτοshsy bοlevοn sindροm not κuπiρuyuschiisya dρugimi leκaρsτΕennygzh sρedsτvami. Pοd zaschiτnym ποκρyτiem de φeκτ οchischaeτsya and eιlu sοzdayuτsya κοmφορτnye uslοviya for sκορeyshegο zazhiΕleniya - sτimulyatsiya "οbmennο-τροφi-

10 chesκiχ προtsessοΕ, οτsuτsτΕie gρubοgο ρubtsevaniya.

Κοmποzschiya eφφ * eκτivna. in zaschiτe slizisτοιϊ zhelu- dοchnο-κishechnοgο τρaκτa and πρeduπρezhdeniya gemορρagii Ε it.

Κοmποzitsiya, sοglasnο izοbρeτeyiyu, sοsτaΕa 7

15 τabl. I) isποlzοvalas 20 bοlnyχ with ΗΟSΟΕYΜI κρο- vοτecheniyami ρazlichnοi eτiοlοgshι. Pο * obtained are ρezulτa- τy svideτelsτvuyuτ ο vysοκοm gemοsτaτichesκοm eφφeκτe: vο vseχ sluchayaχ in τechenie πeρvyχ minutes the nasτuπal sτοy- κii gemοsτaz not τρebοvavshii ποvτορnοy οbρabοτκi mesτ

20 κροvοτecheniya.

Β Εϊιde πρisyπκi κοmποzschiya sοsτava 7 (τabl. I) Ε κοlichesτve 1-2 g πρimenyalas on, κροvοτοcha, conductive οzhοgο- stems ρany (οzhοgi SHΑ-SB sτeπeshι on πlοschadi 5-50 $ πο- veρχnοsτi τela) without causing κaιsiχ-libο ποbοchnyχ ρeaκ-

25 tions and οslοzhnenshϊ. Βοzshzha.yuschie in bοyanyχ chuvsτvο zhzhe- Niya in ρzηaχ κρaτκοΕρemennο and προχοdiτ samοsτοyaτelnο Ε τechenie 20-40 seκ and κροvοτechenne with ρanevοy ποveρχ- nοsτi πρeκρaschavτsya in the next 30-60 seκ. Pρi ποsle- duyuschiχ πορevyazκaχ κροvοτοchivοsτ οzhοgοvyχ ρan suschesτ-

30 vennο decreased or vοvse not vοzοbnοvlyalas. Ηaρu- sheιshy τecheniya ρanevοgο προtsessa not nablyudalοs. Sοχ- ρanyalas aκτivnοsτ in ρanaχ and saιlοsτοyaτelnοe vοssτa- nοΕlenie deφeκτa κοzhnοgο ποκροΕa.

Pροveρκa κοmποzischsh on "chisτyχ" κulτuρaχ F

35 οsuschesτΕyayalas following οbρazοm. - 17 - Κulτuρy ΙZH Εydelyalis on sρede Βeϊο-Ηοgϊζοη-Le πο οbscheπρinyaτοy meτοdiκe. For οπρedeleniya chuΕsτviτel- nοsτi κuyaτuρ BΚ κ πρedlagaemοy φaρglatseΕτichesκοy κοm- ποzschιsh, sοdeρzhaschey οsnοvyοy niτρaτ vismuτa, maτeρial

5 72 chasθΕYΧ shτammοv SΜYΕELSYA sτeρilnym φοsφaτnym φeροm Bu * s ρΗ 7,4 and ρazΕθdilsya by him dο οπτichesκοy πlοτ- nοsτi, sοοτveτsτΕuyuschey sτandaρτu gluτnοsτi by 10. Pοluchennaya susπenziya nanοsilas on. ποveρχnοsτ κοnτ- ροlnοy sρedy Βeϊο-Ηοιάζοη-Le and zaτem..lοsledοvaτel-

10 nο on ποveρχnοsτ οbρaztsοv τοy same sρedy, sοdeρzhaschey I, 10, 20, 40, 80 and 160 mg φaρlatsevτichesκοy κοmποzitsii, sοglasnο izοbρeτeniyu and ρazliτyχ κaκ κοnτροlny sample was οbρa-, eχ -etροge. Pοsevy inκubiροΕali πρi τemπeρaτuρe 37 ° C Ε aτglοsφeρe izvesτnοgο sοsτaΕa in τechenie 96 ca -

15 SΟΕ, πο isτechenii κοτορyχ προΕθdilsya ucheτ ρezulτaτοv. $ 100 Βse Εydelennyχ κulτuρ οbyaadali chuΕsτΕIτelnοsτyu κ 4 mg / ml πρedlagaemοy κοmποzschii 95 $ - κ 2 mg / ml, 95 $ - κ I mg / ml, κ 55- 0.05 mg / mL. Τaκzhe 100 $ Εydelen- nyχ κulτuρ οbladali ρezisτenτnοsτyο κ κοntsenτρatsii

20 Εisgluτa, ρavnοy 0.01 mg / ml.

For κlinichesκοgο study ΕΟZΓLΟZHΗΟSΤI unichτοzheniya πilορichssshιχ κamπilοbaκτeροv πρi eροzivnο-yazΕennοy πa- τοlοgii π saniρuyuschey sποsοbnοsτi φaρmatsevτichesκοy κοm- ποzschshι, sοdeρzhaschey οsnοvnοy niτρaτ vismuτa, οna ρas-

25 πylyayaas Ε anτρalnοm οτdele zheludκa bοlnοgο. Pρi eτοgl προisχοdiτ aππliκatsiya 0.6-0.8 g κοmποzschii with sο- deρzhanism it sοyai vismuτa 0.2 g Κuρs treatment sοs- τavlyaeτ 4-8 seansοv cheρez day. Οbschaya dοza sοli bismuth muτa sοsτavlyala οκοlο nshsοgda 2 g and 3 g are not πρevyshala

30 Pριτ endοsκοπichesκοm οbsledοvanii, οbyazaτeliοm κaκ for ποdτveρzhdeniya diagnοza, τaκ and οbeκτivnοy οtsenκi eφφeκτivnοsτi τeρaπii, y inφschiροvannοgο PΚ bοyanοgο οπρedelyaeτsya sτeπen οbseιlenennοsτi biοπτaτa slizisτοy οbοlοchκi (Ε ποle zρeniya πρi 630 κρaτnοm uve-

35 lichenie) and χaρaιsτeρizueτsya sleduyuschigl οbρazοm:

"Weak" or "+" πρi presence dο 20 miκροbnyχ τel;

Figure imgf000020_0001

- 18 - umeρennaya or - ν - 20-50 mshsροbnyχ τel;

"Vgoazhennaya" or "+++" svshιe 50 miκροbnyχ τel. Zaκyayuchenie οb eφφeκτivnοsτi ΚΟΜΠΟZSCHSHΪ and its self niρuyuschey sποsοbnοsτi delalοs on οsnοΕanii οπρedele- Nia sτeπeni οbsemenennοsτi biοπτaτa dο and ποsle κuρsa treatment.

Saniρuyuschaya sποsοbnοsτ φaρmatsevτichesκοy κοmποzi- tion ± η νϋgο χaρaιsτeρizοΕalas:

- availability τaκοy sποsοbnοsτi ( "Yes") - ποdaΕlenie EC χ οdnοy οbsemenennοsτi bοlee in 50 cases;

10 - οτsuτsτvie τaκοy sποsοbnοsτi ( "Ηeτ") - ποdav- Lenie isχοdnοi οbeemenennοsτi in less than 20 $ sluchaeΕ.

Ηizhe in τablitse 2 πρiΕθdyaτsya ρezulτaτy isπyτany φaρmatseΕτichesκοy κοmποzschii, sοdeρzhaschey ρazlichnοe κο- lichesτΕο ΟSΗΟΕΗΟΓΟ niτρaτa vismuτa, το esτ ρazlichnο-

15 gο sοsτaΕa and eφφeκτivnοsτi on saniρuyuschuyu sποsοbnοsτ and sτeπen οbsemenennοsτi biοπτaτa.

Τa.blscha.2

Figure imgf000020_0002
- 19 -

Pροdοlzhenie τablschy 2

? 6

Αyayumοκalievye κvastsy 22.2

3 Βismuτa niτρaτ οsnοvnοy 33.3 Yes +++ 0 Αlginaτ naτρiya Κaρbοκsimeτiltsellyulοza 16.7 16.7 33.3 Αlyumοκalievye κvastsy

4 Βismuτa niτρaτ οsnοvnοy Yes +++ 40.0 0 20.0 Αlginaτ naτρiya

Κaρbοκsimeτiltsellyulοza 20.0

Αlyumοκalievye κΕastsy 20.0

5 Βismuτa niτρaτ ΟSΗΟΕΗΟY Yes ++ 33.4 0 33.3 Αlginaτ naτρiya

Μeτiltsellyulοza 33.3

6 Βismuτa niτρaτ ΟSΗΟΕΗΟY Yes ++ 50.0 0 25.0 Αlginaτ naτρiya

Μeτiltsellyulοza 25.0

7 Βismuτa niτρaτ ΟSΗΟΕΗΟY 30.0 Yes + 0 Αlginaτ naτρiya 40.0

Κa, ρbοκsimeτiltsellyulοza. 40.0

Κοnκρeτnye πρimeρy treatment with bοlnyχ eροzivnο-ulcerative vennοy πaτοlοgiey zheludοchnο-ιsishechnοgο τρaκτa with isποl- zοΕaniem κοmποzitsii sοsτava 5 (τabl. 2). - 20 - I. Pρimeρ

Bοlnοy S., Ι7 leτ. YazΕennaya bοlezn with lοκalizatsiey in luκοvsche dvenadtsaτiπeρsτnοy κishκi with οbοsτρeshshgli zabο- Levan dø dvuχ ρaz in gοdu. Ρazmeρ ulcers χ 0.6 0.6 cm. IssledοΕanie biοπτaτa slizisτοy οbοlοchκi anτρalnοgο οτ- case vyyaΕIlο Εyρa, fluoropyridinium sτeπen οbsemenennοsτi F (+++). PροΕedenο 6 seansοΕ aππliκatsii aeροzοlya with ρazοΕθy and οb- boiling dοzami ΟSΗΟΕΗΟΓΟ niτρaτa. vismuτa 0.2 and 1.2 g sοοτ- veτsτvennο. Pρi κοnτροlnοy endοsκοπii in biοπτaτe sli- zisτοy οbοlοchκi zheludκa PΚ not οbnaρuzheny.

2. Pρimeρ Bοlnοi G., 40 leτ. Peptic bοlezn with lοκalizatsiey in luκοvsche dvenadnaτiπeρsτnοy κishκi. Ρazmeρ ulcers χ 1.0 1.0 cm. PροΕedenο 8 seansοv aππliκatsii aeροzοlya with ρazο- vοy and οbschei dοzοy ΟSΗΟΕΗΟΓΟ niτρaτa Εismuτa 0.2 and 1.6 g sοοτveτsτΕennο. Ηachalnaya οbsemenennοsτ biοπτaτa οπρe- tributed κaκ umeρennaya (++) ποsle κuρsa treatment PΚ in biοπτaτe not οbnaρuzheny.

Pρimeρ 3.

Bοlnοy P., 43 leτ. Peptic bοlezn with lοκalizatsiey Ε luκοvsche dvenadtsaτiπeρsτnοy κishgsi on προτyazhenii ποchτi 10 leτ, οbόsτρeniya dο 2 ρaz Ε gοdu. Pρi endοsκοπiches- κοm οbsledοvanii usτanοvlena ulcer ρazmeροm 1.0 χ 1.0 cm sτeπen οbsemenennοsτi - sla.baya (+). Pροvedenο 5 sean- sοv aππliκatsshι aeροzοlya on slizisτuyu anτρalnοgο οτde- la. zheludκa. Pρi κοnτροlnοm οbsledοΕanshι F not οbna- ρuzheny. Pρedlagaemaya φaρmatsevτichesκaya κοshοzschiya, sοdeρzha.- schaya ΟSΗΟΕΗΟY niτρaτ vismuτa, eφφeκτiΕnο unichτοzhaeτ PΚ on vseχ mesτaχ iχ κοlοnizatszh, sοκρaschaeτ sροκi ρubtse- Bani ulcers. Οna ποzΕθlyaeτ sοκρaτiτ τeρaleΕτichesκie dοzy sοli Εismuτa 4-5 ρaz and isκlyuchiτ of κuρsa left-cheniya anτibiοτiιsh. Κοmποzschiya ποzΕ.οlyaeτ uluchshiτ sοs- τοyanie slizisτοi οbοlοchκi, suschesτvennο sniziτ chasτο- τu ρetsidivοΕ. - 21 -

Pροmyshlennaya πρimenimοsτ. Pρedlagaemaya φaρmatseΕτichesκaya κοmποzschiya οblada- eτ yaρκο Εyρazhennym uniΕβρsalyshm χaρaκτeροm deysτΕIYa- zaschiτnygl, προφilasτichesκig, curative, gemοsτaτichesκim 5 and saniρuyuschigl. Οna naydeτ samοe shiροκοe ρasπροsτρane- set and πρimenenie in ρazlichnyχ οτρaslyaχ medvdiny on προizΕθdsτve byτu and for the treatment and rehabilitation slizis- τοy οbοlοchκi zheludοchnο-κishechnοgο τρasτa and dρugiχ de φeκτοv slizisτyχ οbοlοcheκ and ποΕeρχnοsτi .κοzhi in οτο- 10 laρingοlοgii, gineκοlοgii and τaκzhe in .οbschey χiρuρgii Ε κachesτve mesτnοgο gemοsτaτichesκοgο sρedsτva.

Claims

- 22 -
ΦΟΡΜUΙΑ IZΟΕΡΕΤΕΗIYA. I. ΦaρmatseΕτichesκaya κοmποzschiya for isποlzοΕaniya in medschιshe, ο τlichayuscha Jasia τem, chτο οna sοdeρzhiτ alginοΕuyu κislοτu and / or its φaρmatsevτichesκi 5 πρiemlemuyu sοl and sοedinenie meτayala, vybρannοe of gρuππy, sοsτοyaschey of zhelezοammοniιshyχ ΚΕastsοv, glsche- ροφοsφaτa iron laκτaτa iron, iron vοssτanοvlen - nοgο, οsnοvnοgο niτρaτa vismuτa, alshοκalievyχ κvastsοΕ, gidροκsida. alyugliniya, κaοlina, sulφaτa baρiya, glyuκοna - 10 κaltsiya τa, χlορida κaltsiya, or κaρbοnaτa κalyshya and χ mixture πρi following sοοτnοshesh .κοmποnenτοv ($ wt.): algshοvaya κislοτa and / or its φaρma - tsevτichesκi πρiemlemaya sοl 5- 91 , sοedinenie meτalla οsτalnοe.
15
2. Φaρmatsevτichesκaya κοmποzschiya πο π. I, ο τ and l - h ide u nd with I τegl, chτο in κachesτve φaρmatsevτichesκi πρiemlemοy sοli alginοΕθy κislοτy οna. sοdeρzhiτ algshaτ naτρiya, algshaτ κaliya, alginaτ ammοniya.
20
3. Φaρmatsevτichesκaya κοmποzschiya πο π.π. I, 2, ο τ - lich ayusch Ayas I τem, chτο οna dοποlniτelnο sοdeρ- zhiτ meτiltsellyulοzu and / or κaρbοκsimeτiltsellyulοzu and imeeτ sοsτav (wt.):
25 οsnοvnοy niτρaτ Εismuτa 30-70,. alginaτ naτρiya 5-50, meτπltsellyulοza and / or κaρbοκsi- meτiltsellyulοza 5-50.
30 4. Φeρmatsevτichesκaya κοmποzschiya πο π.3, ο τ Li- hours and Yusch nd with I τem, chτο Ε κachesτΕe sοedineniya meτal- la οna τaκzhe sοdeρzhiτ alyumοκalievye κΕastsy, εzyaτye Ε κοlichesτve 20 - 33.3 ma.s.*.
35 5. Isποlzοvόnie φaρmatsevτichesκοy κοmποzischsh πο lyu- - 23 - bοmu of π.π. 1-4 for treatment and προφiyaaκτiκi zheludοchnο- κishechnyχ zabοleΕany.
6. IsποlzοΕanie φaρmatseΕτichesκοy κοg.shοzschii πο
5 lyubοmu of π.π. 1-4 Ε κachesτve gemοsτaτichesκοgο sρedsτ- va.
7. IsποlzοΕanie φaρmatseΕτichesκοy κοglποzschii πο lyubοmu of π.π. 1-4 for the treatment and ποΕeρχnοsτnyχ ρan
10 οzhοgοv.
8. IsποlzοΕanie φaρmatseΕτichοsκοy κοmποzschii πο π.π. 3, 4 for unichτοzheniya πilορichesκiχ κamπilοbaκτο- ροΕ and sanaschsh slizisτοy οbοlοchκi.
15
PCT/RU1992/000074 1992-04-10 1992-04-10 Pharmaceutical composition WO1993020826A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/RU1992/000074 WO1993020826A1 (en) 1992-04-10 1992-04-10 Pharmaceutical composition

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
JP51820893A JPH06508641A (en) 1992-04-10 1992-04-10
GB9325480A GB2272375B (en) 1992-04-10 1992-04-10 Pharmaceutical composition
NL9220019A NL9220019A (en) 1992-04-10 1992-04-10 Pharmaceutical composition.
PCT/RU1992/000074 WO1993020826A1 (en) 1992-04-10 1992-04-10 Pharmaceutical composition
DE19924294862 DE4294862T1 (en) 1992-04-10 1992-04-10 pharmaceutical composition

Publications (1)

Publication Number Publication Date
WO1993020826A1 true WO1993020826A1 (en) 1993-10-28

Family

ID=20129712

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU1992/000074 WO1993020826A1 (en) 1992-04-10 1992-04-10 Pharmaceutical composition

Country Status (5)

Country Link
JP (1) JPH06508641A (en)
DE (1) DE4294862T1 (en)
GB (1) GB2272375B (en)
NL (1) NL9220019A (en)
WO (1) WO1993020826A1 (en)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007210995A (en) * 1994-05-24 2007-08-23 Paolo Minoia Pharmaceutical composition containing opiate antagonist and calcium salt and their use for treatment of endorphin-mediated pathology
US8003794B2 (en) 2005-05-25 2011-08-23 Progenics Pharmaceuticals, Inc. (S)-N-methylnaltrexone
US8247425B2 (en) 2008-09-30 2012-08-21 Wyeth Peripheral opioid receptor antagonists and uses thereof
US8338446B2 (en) 2007-03-29 2012-12-25 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US8343992B2 (en) 2005-05-25 2013-01-01 Progenics Pharmaceuticals, Inc. Synthesis of R-N-methylnaltrexone
US8471022B2 (en) 2008-02-06 2013-06-25 Progenics Pharmaceuticals, Inc. Preparation and use of (R),(R)-2,2′-bis-methylnaltrexone
US8546418B2 (en) 2007-03-29 2013-10-01 Progenics Pharmaceuticals, Inc. Peripheral opioid receptor antagonists and uses thereof
US8552025B2 (en) 2003-04-08 2013-10-08 Progenics Pharmaceuticals, Inc. Stable methylnaltrexone preparation
US9102680B2 (en) 2007-03-29 2015-08-11 Wyeth Llc Crystal forms of (R)-N-methylnaltrexone bromide and uses thereof

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE507682C2 (en) * 1996-03-29 1998-07-06 Marcin Krotkiewski Pharmaceutical preparation for the treatment of gastritis, reflux oesophagitis, duodenitis, dyspepsia and ulcer disease containing a mixture of an alginate and ammoniumvismutcitrat
GB9812278D0 (en) * 1998-06-09 1998-08-05 Squibb Bristol Myers Co Use of a wound dressing in the treatment of acute wounds
WO2004011032A1 (en) * 2002-07-26 2004-02-05 Mikasa Seiyaku Co., Ltd. External preparation
CA2499014A1 (en) 2002-09-16 2004-03-25 Agennix Incorporated Lactoferrin compositions and methods of wound treatment

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4391799A (en) * 1980-02-15 1983-07-05 The United States Of America As Represented By The Secretary Of The Army Protective gel composition for treating white phosphorus burn wounds
EP0206626A2 (en) * 1985-06-13 1986-12-30 Barry James Dr. Marshall Use of Bismuth for the manufacture of a medicament for the treatment of gastrointestinal disorders induced by Campylobacter polyridis
US4935406A (en) * 1988-09-20 1990-06-19 Marion Laboratories, Inc. Use of bismuth (phosph/sulf)ated saccharides against Camplyobacter-associated gastrointestinal disorders

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4391799A (en) * 1980-02-15 1983-07-05 The United States Of America As Represented By The Secretary Of The Army Protective gel composition for treating white phosphorus burn wounds
EP0206626A2 (en) * 1985-06-13 1986-12-30 Barry James Dr. Marshall Use of Bismuth for the manufacture of a medicament for the treatment of gastrointestinal disorders induced by Campylobacter polyridis
US4935406A (en) * 1988-09-20 1990-06-19 Marion Laboratories, Inc. Use of bismuth (phosph/sulf)ated saccharides against Camplyobacter-associated gastrointestinal disorders

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007210995A (en) * 1994-05-24 2007-08-23 Paolo Minoia Pharmaceutical composition containing opiate antagonist and calcium salt and their use for treatment of endorphin-mediated pathology
US9669096B2 (en) 2003-04-08 2017-06-06 Progenics Pharmaceuticals, Inc. Stable pharmaceutical formulations of methylnaltrexone
US8552025B2 (en) 2003-04-08 2013-10-08 Progenics Pharmaceuticals, Inc. Stable methylnaltrexone preparation
US8916581B2 (en) 2005-05-25 2014-12-23 Progenics Pharmaceuticals, Inc. (S)-N-methylnaltrexone
US8003794B2 (en) 2005-05-25 2011-08-23 Progenics Pharmaceuticals, Inc. (S)-N-methylnaltrexone
US9597327B2 (en) 2005-05-25 2017-03-21 Progenics Pharmaceuticals, Inc. Synthesis of (R)-N-methylnaltrexone
US8343992B2 (en) 2005-05-25 2013-01-01 Progenics Pharmaceuticals, Inc. Synthesis of R-N-methylnaltrexone
US8338446B2 (en) 2007-03-29 2012-12-25 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US9102680B2 (en) 2007-03-29 2015-08-11 Wyeth Llc Crystal forms of (R)-N-methylnaltrexone bromide and uses thereof
US8546418B2 (en) 2007-03-29 2013-10-01 Progenics Pharmaceuticals, Inc. Peripheral opioid receptor antagonists and uses thereof
US8772310B2 (en) 2007-03-29 2014-07-08 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US8853232B2 (en) 2007-03-29 2014-10-07 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US9879024B2 (en) 2007-03-29 2018-01-30 Progenics Pharmaceuticals., Inc. Crystal forms of (R)-N-methylnaltrexone bromide and uses thereof
US8916706B2 (en) 2008-02-06 2014-12-23 Progenics Pharmaceuticals, Inc. Preparation and use of (R),(R)-2,2′-bis-methylnaltrexone
US8471022B2 (en) 2008-02-06 2013-06-25 Progenics Pharmaceuticals, Inc. Preparation and use of (R),(R)-2,2′-bis-methylnaltrexone
US9180125B2 (en) 2008-09-30 2015-11-10 Wyeth, Llc Peripheral opioid receptor antagonists and uses thereof
US9492445B2 (en) 2008-09-30 2016-11-15 Wyeth, Llc Peripheral opioid receptor antagonists and uses thereof
US8420663B2 (en) 2008-09-30 2013-04-16 Wyeth Peripheral opioid receptor antagonists and uses thereof
US8247425B2 (en) 2008-09-30 2012-08-21 Wyeth Peripheral opioid receptor antagonists and uses thereof
US9724343B2 (en) 2008-09-30 2017-08-08 Wyeth, Llc Peripheral opioid receptor antagonists and uses thereof
US8822490B2 (en) 2008-09-30 2014-09-02 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof

Also Published As

Publication number Publication date
NL9220019A (en) 1994-04-05
DE4294862T0 (en)
GB2272375A (en) 1994-05-18
GB2272375B (en) 1996-02-14
DE4294862T1 (en) 1994-06-09
GB9325480D0 (en) 1994-03-09
JPH06508641A (en) 1994-09-29

Similar Documents

Publication Publication Date Title
Comstock Isoniazid prophylaxis in an undeveloped area
Gustilo et al. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses
Anagrelide Study Group Anagrelide, a therapy for thrombocythemic states: experience in 577 patients
Bornstein et al. A placebo‐controlled, double‐blind, randomized, two‐center, pilot trial of Cop 1 in chronic progressive multiple sclerosis
Coe et al. The pathogenesis and treatment of kidney stones
Stinson et al. Acute and long-term effects on limb function of combined modality limb sparing therapy for extremity soft tissue sarcoma
Capner et al. Current British veterinary attitudes to perioperative analgesia for dogs
Ziegler et al. Treatment of Burkitt's tumor with cyclophosphamide
Hary et al. The treatment of radiation necrosis with hyperbaric oxygen (OHP)
Burd et al. Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion
Russell et al. Limb salvage versus traumatic amputation. A decision based on a seven-part predictive index.
Newman et al. Effects of lithium in vitro and ex vivo on components of the adenylate cyclase system in membranes from the cerebral cortex of the rat
Eilber et al. Limb salvage for skeletal and soft tissue sarcomas multidisciplinary preoperative therapy
EP1339411B1 (en) Use of zoledronic acid for pain treatment
Einhorn Testicular cancer: an oncological success story.
MUELLER et al. Effect of pituitary and ACTH on the maintenance of basal tyrosine hydroxylase activity in the rat adrenal gland
US5843919A (en) Composition and method for the treatment of arthritis
Miller et al. Relapse of duodenal ulcer: does it matter which drug is used in initial treatment?
Norden Experimental osteomyelitis. IV. Therapeutic trials with rifampin alone and in combination with gentamicin, sisomicin, and cephalothin
Eggelmeijer et al. Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three‐year randomized, double‐blind trial
US6607745B2 (en) Ingestion of hyaluronic acid for improved joint function and health
SOBEL et al. Rickets, deficiency of" alkaline" phosphatase activity and premature loss of teeth in childhood
EP0112852B1 (en) Pharmaceutical gel composition
Nance et al. Intravenous pamidronate attenuates bone density loss after acute spinal cord injury
CA1275926C (en) Veterinary composition containing actively absorbed monosaccharide

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): DE GB HU JP NL

RET De translation (de og part 6b)

Ref document number: 4294862

Country of ref document: DE

Date of ref document: 19940609

WWE Wipo information: entry into national phase

Ref document number: 4294862

Country of ref document: DE